Desenvolvimento de um modelo animal de câncer de pênis HPV negativo: Potencial efeito do tratamento crônico com composto isolado da Scoparia dulcis L.

Abstract

Introduction: Penile cancer is a serious public health problem in North and Northeast Brazil. The current classification of the World Health Organization considers that there are two pathways of penile carcinogenesis, one associated with human papillomavirus (HPV) and another, less well characterized, independent of HPV, which is speculated to be induced by chronic inflammation. Furthermore, there are few treatment options to reduce lesions in this context. The present work aimed to develop an HPV independent model of penile carcinogenesis, testing the hypothesis that chronic inflammation induces penile cancer and evaluating the potential effect of treatment with the isolated compound Cirsitakaoside (Cirsimarina). Methods: Forty male Wistar rats aged 8 weeks were divided into 6 experimental groups, exposed topically on the glans penis to saline (Control group), an inflammatory agent (carrageenan, CG), a mutagen (4-nitroquinoline, 4NQO) and both products. Two groups exposed to GC and 4NQO also received a natural compound with anti-inflammatory properties, cirsimarine (0.5mg/Kg and 1.0mg/Kg). The treatment was carried out for 12 weeks. The macroscopic appearance of the penis and the temperature of the pelvic region were evaluated using photographic and thermographic techniques. The following organs were collected: penis, tongue, heart, lung, kidney, spleen, liver, thymus, adrenals, testes, prostate and adipose tissue and the blood of the animals. The penis was processed for histological analysis to identify the lesions, and the internal organs were weighed. Blood samples were used to determine circulating values of total cholesterol, magnesium and albumin. Results: Macroscopic analysis showed the development of inflammation in the glans and prepuce of animals exposed to GC and 4NQO, however, those treated with cirsimarine had a decrease in the inflammatory process. However, regarding the thermographic analysis, no significant changes were observed. As for the histological analysis, hyperplasia of the preputial epithelium was observed and one animal developed penile intraepithelial neoplasia (PeIN), and these alterations were observed mainly in the groups treated with CG and 4NQO. Animals treated with cirsimarine did not develop proliferative lesions. Cirsimarine also reduced body weight, fat mass and total cholesterol, increased thymus and adrenal weights, and reduced liver, kidney and testicular weights. Conclusions: The administration of CG and 4NQO resulted in a high incidence of chronic inflammation of the penis and foreskin and a low incidence of proliferative lesions, supporting the hypothesis that inflammation promotes penile carcinogenesis, as well as the anti-inflammatory effect of Cirsimarin.